High IGSF4 expression in pediatric M5 acute myeloid leukemia with t(9;11)(p22;q23)
Abstract
Pediatric mixed-lineage leukemia (MLL)-rearranged acute monoblastic leukemia with t(9;11)(p22;q23) has a favorable outcome compared with other MLL-rearranged AML. The biologic background for this difference remains unknown. Therefore, we compared gene expression profiles (GEPs; Affymetrix HGU133 + 2.0) of 26 t(9;11)(p22;q23) patients with 42 other MLL-rearranged AML patients to identify differentially expressed genes. IGSF4, a cell-cell adhesion molecule, was found to be highly expressed in t(9;11)(p22;q23) patients, which was confirmed by real-time quantitative polymerase chain reaction and Western blot. IGSF4 expression within t(9;11)(p22;q23) patients was 4.9 times greater in French-American-British morphology classification (FAB)-M5 versus other FAB-types (P = .001). Methylation status investigation showed that high IGSF4-expressing t(9;11)(p22;q23) patients with FAB-M5 have no promoter hypermethylation, whereas all other cases do. Cell-line incubation with demethylating agent decitabine resulted in promoter demethylation and increased expression of IGSF4. Down-regulation of IGSF4 by siRNA did not affect proliferation or drug sensitivity. In a cohort of 79 MLL-rearranged AML cases, we show significant better overall survival for cases with high IGSF4 expression (5-year overall survival 0.70 vs 0.37, P = .03) In conclusion, we identified IGSF4 overexpression to be discriminative for t(9;11)(p22;q23) patients with FAB-M5, regulated partially by promoter methylation and resulting in survival benefit.
| Authors: | Kuipers JE, Coenen EA, Balgobind BV, Stary J, Baruchel A, de Haas V, de Bont ES, Reinhardt D, Kaspers GJ, Cloos J, Danen-van Oorschot AA, den Boer ML, Marschalek R, Meyer C, Pieters R, Zwaan CM, van den Heuvel-Eibrink MM |
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| Journal: | Blood. 20;117(3):928-35 |
| Year: | 2011 |
| PubMed: | Find in PubMed |